Tricyclic Antidepressant Amitriptyline Indirectly Increases the Proliferation of Adult Dentate Gyrus-Derived Neural Precursors: An Involvement of Astrocytes

Boku, Shuken; Hisaoka-Nakashima, Kazue; Nakagawa, Shin; Kato, Akiko; Kajitani, Naoto; Inoue, Takeshi; Kusumi, Ichiro; Takebayashi, Minoru

Tricyclic Antidepressant Amitriptyline Indirectly Increases the Proliferation of Adult Dentate Gyrus-Derived Neural Precursors: An Involvement of Astrocytes

Boku, Shuken; Hisaoka-Nakashima, Kazue; Nakagawa, Shin et al.

Plos one, 2013, 8(11), e79371

Permalink : https://hdl.handle.net/2115/54114

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アクセス権	open access
URI	https://hdl.handle.net/2115/54114
タイトル	Tricyclic Antidepressant Amitriptyline Indirectly Increases the Proliferation of Adult Dentate Gyrus-Derived Neural Precursors: An Involvement of Astrocytes
著者	Boku, Shuken ; Hisaoka-Nakashima, Kazue ; Nakagawa, Shin ; Kato, Akiko ; Kajitani, Naoto ; Inoue, Takeshi ; Kusumi, Ichiro ; Takebayashi, Minoru
e-Rad_Researcher 60455665 著者名 Boku, Shuken
著者名 Hisaoka-Nakashima, Kazue
e-Rad_Researcher 60360905 著者名 Nakagawa, Shin
著者名 Kato, Akiko
著者名 Kajitani, Naoto
e-Rad_Researcher 70250438 著者名 Inoue, Takeshi
e-Rad_Researcher 30250426 著者名 Kusumi, Ichiro
著者名 Takebayashi, Minoru
言語	英語
発行日	2013-11-18
出版者	Public library science
収録物名	Plos one
巻(号)	8(11)
ページ	e79371
抄録	Antidepressants increase the proliferation of neural precursors in adult dentate gyrus (DG), which is considered to be involved in the therapeutic action of antidepressants. However, the mechanism underlying it remains unclear. By using cultured adult rat DG-derived neural precursors (ADP), we have already shown that antidepressants have no direct effects on ADP. Therefore, antidepressants may increase the proliferation of neural precursors in adult DG via unknown indirect mechanism. We have also shown that amitriptyline (AMI), a tricyclic antidepressant, induces the expressions of GDNF, BDNF, FGF2 and VEGF, common neurogenic factors, in primary cultured astrocytes (PCA). These suggest that AMI-induced factors in astrocytes may increase the proliferation of neural precursors in adult DG. To test this hypothesis, we examined the effects of AMI-induced factors and conditioned medium (CM) from PCA treated with AMI on ADP proliferation. The effects of CM and factors on ADP proliferation were examined with BrdU immunocytochemistry. AMI had no effect on ADP proliferation, but AMI-treated CM increased it. The receptors of GDNF, BDNF and FGF2, but not VEGF, were expressed in ADP. FGF2 significantly increased ADP proliferation, but not BDNF and GDNF. In addition, both of a specific inhibitor of FGF receptors and anti-FGF2 antibody significantly counteracted the increasing effect of CM on ADP proliferation. In addition, FGF2 in brain is mainly derived from astrocytes that are key components of the neurogenic niches in adult DG. These suggest that AMI may increase ADP proliferation indirectly via PCA and that FGF2 may a potential candidate to mediate such an indirect effect of AMI on ADP proliferation via astrocytes.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 3.0 Unported
PISSN	1932-6203
関連情報	PMID 24260208
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1371/journal.pone.0079371